Walter Jacobs Was a Very Highly Regarded Member of the Rockefeller Institute for Some Fifty Years

Home , Hederagenin, Louise Pearce, Sarsasapogenin

NATIONAL ACADEMY OF SCIENCES

WALTER ABRAHAM JACOBS

1883—1967

A Biographical Memoir by ROBERT C. ELDERFIELD

Any opinions expressed in this memoir are those of the author(s) and do not necessarily reﬂect the views of the National Academy of Sciences.

Biographical Memoir

WALTER ABRAHAM JACOBS December 24, 1883-July 12, 1967

BY ROBERT C. ELDERFIELD

ALTER ABRAHAM JACOBS died in Los Angeles after a Wlong and impressive career. He left behind some 273 publications which record important contributions in the field of the chemistry of natural products of biological im- portance, as well as the development of chemotherapeutic agents-the significance of which was not recognized until some years had passed. Jacobs was born in New York City on December 24, 1883 and attended local elementary schools. He received an A.B. degree in 1904 and an A.M. in 1905 from Columbia Univer- sity, after which he enrolled at the University of Berlin for study under Emil Fischer, earning a Ph.D. degree in 1907. On his return to New York, Jacobs received an appoint- ment as a fellow in chemistry in the laboratory of Phoebus A. Levene at the newly established Rockefeller Institute for Medical Research. In 1908 he became an assistant, and in 1910 an associate in Levene's laboratory. During these years with Levene, he was closely associated with the latter's work on the chemistry of the nucleic acids. The studies, first with the nucleotide inosinic acid from beef extract, disclosed its essential chemistry by hydrolysis to the nucleoside, inosine, and by subsequent cleavage from the latter of its crystalline sugar component which was identified 248 BIOGRAPHICAL MEMOIRS as D-ribose. This became the pattern for similar studies with the nucleotide guanylic acid, and with yeast nucleic acid (ribonucleic acid), from which the various nucleosides were then isolated and interpreted. The attempted extension of this procedure to similar studies with thymus nucleic acid (subsequently shown to be desoxyribosenucleic acid) was interrupted by Jacobs' promotion in 1912 to associate member of the Institute with independent status. Dr. Simon Flexner, Director of the Institute, felt that the developing field of chemotherapy warranted a division of its own, and Jacobs was placed in charge of it. In collaboration with Michael Heidelberger, he began an investigation of the possible chemotherapy of polio. It was known that hexamethylenetetramine apparently exerted a slight therapeutic effect, and an extended series of quaternary salts was prepared by reaction with aromatic and alipathic halogen compounds. Some of the salts displayed bactericidal properties, and a few appeared to prolong the life of polio-infected monkeys. Un- fortunately, this was due to a loss of virulence of the virus strain. After the disappointing outcome of the chemotherapeutic studies concerning polio, the JacobsHeidelberger team turned its attention to African sleeping sickness, for which no effective and non-toxic drugs were available. Ehrlich had produced a powerful synthetic agent against trypanosomiasis in para-arsenophenylglycine, in which the arsenic was tri- valent. The analogous pentavalent substance, para-phenylglycine arsonic acid, was considerably less toxic, but devoid of activity against the disease. Jacobs reasoned that the lack of activity could be due to the free carboxyl group which con- ceivably could react with many centers of the tissue proteins before reaching the parasites. He therefore proposed mask- ing the carboxyl group by conversion to the amide. The resulting substance, sodium para-phenylglycine amide ar- WALTER ABRAHAM JACOBS 249 sonate, was the first, simplest, and best arsenical of a series subsequently synthesized. The new arsenical, named Tryparsamide by Simon Flexner, was found to be extremely effective in trypanosome infected animals by Drs. Wade H. Brown and Louise Pearce, who now formed part of the chemotherapeutic team. Several patents were awarded for control of the drug and several of its analogs-although none of the latter proved to be supe- rior to Tryparsamide. At the conclusion of World War I, Louise Pearce made an extensive study of the drug in the Belgian Congo, which showed Tryparsamide to be more effective than previously used drugs. Further tests in the United States demonstrated some utility in the treatment of tertiary syphilis. Some years later (1953), Belgium recognized the successes of Tryparsamide by making Drs. Jacobs, Heidelberger, Brown and Pearce officers of the Order of Leopold 11. During World War I, a portion of the Institute was desig- nated as U.S. Laboratory # 1, and served as a training facility in laboratory techniques for army physicians. Jacobs and Hei- delberger investigated possible synthetic substitutes for Sal- varsan, a drug in scant supply and of undesirable toxicity. One analog (arsenophenyl-glycine-bis-m-hydroxyanilide), which appeared to be less toxic and at least as active against syphilis when studied by Brown and Pearce in animals, showed promising results in some one hundred human syphilitics. Unfortunately, a second batch, for no apparent reason, caused severe, dangerous dermatitis and was abandoned. At the conclusion of the work on arsenicals, Jacobs and Heidelberger desired to turn to fields other than synthetic organic chemistry, but Flexner's faith in this approach pre- vailed and attention was turned to pneumococcal and strep- tococcal infections. The drug, Optochin, had been used with 250 BIOGRAPHICAL MEMOIRS partial success in the treatment of pneumococcal infections, SO further modification of the cinchona alkaloids was investigated, and a long series of papers resulted. Unfortunately, most of these substances killed infected mice faster than drug or infection alone. The state of this area of chemistry in the United States at the time is reflected in the refusal of the Journal of the American Chemical Society to publish the work on the cinchona alkaloids--on the grounds that no one in Amer- ica was interested in alkaloids. Only after long arguments were the manuscripts accepted. One of the intermediates used in modification of the alkaloids and in other syntheses was p-aminobenzene- sulfonamide, or sulfanilamide, which had been prepared in 1908 by Gelmo in Germany. This was shown by Trefouel, Trefouel, Nitti, and Bovet to be one of the metabolic products of the azo dye Prontosil, the antibiotic action of which w,as demonstrated in the same year (1935) by Gerhardt Domagk for which he was awarded the Nobel Prize. Actually, it developed that the antibiotic action of Prontosil was due to the sufanilamide liberated on metabolism of Prontosil. It apparently never occurred to Jacobs and Heidelberger in 1920 that such a simple substance could control bacterial infections by other than direct antibacterial action. If the antibiotic action had been recognized, many thousands of lives could have been saved in the intervening years. After some nine and one-half years, the team of Jacobs and Heidelberger separated. Flexner agreed that chemotherapeutic research through synthetic methods could be abandoned, and Heidelberger was transferred to the new laboratory of Donald D. Van Slyke to become familiar with biochemistry. Jacobs became a full member of the IRocke- feller Institute in 1923, and turned his attention to the eluci- dation of the structures of substances of natural origin which displayed powerful physiological actions in order to correlate WALTER ABRAHAM JACOBS 25 1 structure with such activity. The name of the laboratory was changed to that of chemical pharmacology. The first group explored was that known as the cardiac glycosides, noted for their specific and powerful action on the myocardium, and which are unrivaled in value for the treatment of congestive heart failure. Of the group, the glycosides from digitalis species are probably the best known. Extracts of other plants containing members of the group such as strophanthus species were used as arrow poisons by African tribes. The ancient Egyptians were familiar with the properties of squill, and the Romans used it as an emetic, heart tonic, diuretic and rat poison. Strophanthus was introduced into modern medicine in 1890, and the modern use of digitalis dates from 1785, when William Withering published his famous book entitled, An Account of the Foxglove and Some of Its Medicinal Uses: With Practical Remarks on Dropsy and Other Dis- eases. At the time Jacobs began his investigations on the structures of these important compounds, little was known of them or their chemistry. It was known that they were glycosides consisting of a rather complicated aglycone moiety, which was responsible for their major pharmacological properties, joined with one or more sugar molecules. The digitalis glycosides are present in the plant in extremely small amounts, whereas the seeds of Strophanthus kombi are rela- tively rich in the glycosides of strophanthidin. Jacobs' plan of attack on the structures of the aglycones was to place major emphasis on the structure determination of the more accessible strophanthidin and to attempt a correlation of this structure with the digitalis aglycones and others by chemical inter- conversions of appropriate derivatives. This plan proved to be completely successful and the structures of a half dozen or so of the aglycones were demonstrated. It should be noted that when the study of the cardiac 252 BIOGRAPHICAL MEMOIRS. aglycones was begun (1923), similar studies on cholesterol and the bile acids by Windaus (1903), Diels (1903) and Wie- land (1912) in Germany were also under way. There was no reason to believe that the th'ree groups of substances would ultimately be found to be closely related. Also, with the possible exception of ultraviolet spectroscopy, none of the instru- mental methods, such as infrared spectroscopy, X-ray spectroscopy and nuclear magnetic resonance, were available. Chemical transformations and degradation with subsequent interpretation formed the basis for structural elucidati~on-a long and tedious process at best. Conversion of a strophanthidin derivative to a periplogenin derivative, and correlation of the latter with derivatives of digitoxigenin and gitoxigenin from digitalis followed. Al- though many structural features of the four aglycones were known, the problem of the carbon skeleton remained un- solved. In 1927, Diels and his co-workers heated cholesterol with selenium, thereby dehydrogenating it to its basic carbon ring system, cyclopentanophenanthrene. Similar dehydrogenation of strophanthidin also yielded Diels' hydrocarbon, thus providing conclusive evidence that the basic ring system of the cardiac aglycones was, indeed, identical with that of cholesterol and the bile acids. With the aid of X-ray data, the latter basic ring system was shown to be that of the Diels' hydrocarbon, a perhydrocyclopentanophenanthrene, by British workers. The problem of the location of the unsaturated lactone side chain on the nucleus of the aglycones was resolved by application of the Barbier-Wieland degradation, useld suc- cessfully in degradation of the side chain of cholanic acid, to a derivative of digitoxigenin with the formation of etiocholanic acid as the final product. Almost simultaneously, R. Tschesche in Germany accomplished a similar degradation WALTER ABRAHAM JACOBS 253 of another aglycone, uzarigenin, to allo-etiocholanic, the dif- ference being in the stereo configuration of the lactone side chain at the 17-position of the nucleus. Although all available evidence up to the actual Barbier- 'Wieland degradation appeared to involve the 17-position as the point of attachment of the side chain, Jacobs, a most meticulous planner of experiments, was loath to attempt the degradation of the side chain. A suitable derivative of the available strophanthidin was not available, and only a few hundred milligrams of an appropriate digitoxigenin derivative were available for the three-step degradation and charac- terization of the product. Jacobs was hesitant to commit this hard to obtain substance to a degradation-the outcome of which, despite its logical prediction, was not certain. It so happened that the necessity for this decision arose early in the fall of 1934. Jacobs and his wife habitually took long Columbus Day weekends to admire the fall foliage of the Adirondack Mountains-and this author took the opportu- nity to commit the entire supply of digitoxigenin derivative to the degradation, with considerable trepidation. After three days and nights, pure samples of etiocholanic acid and its methyl and ethyl esters awaited Jacobs' return. Although the physical constants of all these agreed with the published data, Jacobs, after some hesitation, agreed to request authentic samples from Wieland in Munich for comparison. All compounds were identical with the samples, and this author heaved a sigh of relief. With one minor revision, involving the position of the double bond in the unsaturated lactone side chain, the structure of the cardiac aglycones was established. During his investigations of the cardiac aglycones, Jacobs began structural studies of the saponin group. These are plant glycosides that possess the distinctive property of form- 254 BIOGRAPHICAL MEMOIRS ing a soapy lather in water. The plant heart drugs also display this property, but are classified separately because of their distinctive physiological heart action. Early emphasis was placed on the readily available sarsasapogenin from Smilax ornata Hooker. The aglycone occurs as a glycoside with two rhamnose and one glucose units. The empirical formula of the aglycone was revised to the now accepted C27H4403.Reinvestigation of the selenium dehydrogenation of sarsasapogenin resulted in the isolation of Diels' hydrocarbon, thus establishing that the sapogenins possess the steroid ring system. The presence of a C, side chain was indicated by the isolation of a ketone C8HI6O,which was not identical with methyl isohexyl ketone from cholesterol. A partial structure for sarsasapogenin was suggested in 1935. By this time, great emphasis had been placed on the cortical steroid hormones and their possible therapeutic applica- tions. This resulted in a hectic search for accessible plant sl-eroids which could be converted to cortical hormones. Several investigators, amply financed by the pharmaceutical industry, entered the field. Jacobs, with his small staff, was literally snowed under. However, one further correlation was accom~plished --that of sarsasapogenin with the representative steroid alkaloid, solanidine. By this correlation, the structure of solanidine was established and another member of the steroid group was recognized. Beginning in 1932, an intensive study of the structures of the ergot alkaloids was undertaken in cooperation with the late Dr. Lyman C. Craig. Ergot is the product of a fungus which grows on grain, particularly on rye. Its effect on pregnancy has been known for 2,000 years and it was first used by physicians as an oxytocic agent some 400 years ago. C:onsumptionof edible grain contaminated by the fungus has resulted in death and destruction for centuries. but it was not WALTER ABRAHAM JACOBS 255 recognized as the agent responsible for destructive epidemics until 1670. It was first employed by a physician about 1815, although it had been used by midwives long before. At the time this investigation was undertaken, the chemistry of the ergot group was almost completely unknown. By 1934, on hydrolysis of the alkaloids, a substance named lysergic acid, which proved to be the characteristic building block of the ergot alkaloids, was isolated. The other products of hydrolysis of the alkaloids were amino acid derivatives joined by peptide linkages to themselves and to lysergic acid. The structure of lysergic acid was then shown by degradation and substantiated by subsequent synthesis of the dihydro derivative and of lysergic acid itself. In this work an un- natural amino acid was encountered for the first time. Subse- quently, the now famous L.S.D., the diethyl amide of lysergic acid, was synthesized by A. Hoffmann and Arthur Stoll in Switzerland. The suspicion that such substances might be of more widespread occurrence formed the basis for a plan to extend such studies to other poisonous fungi such as Amanita mus- curia. Although begun, this was interrupted by other work and has since been carried on in other laboratories. The ergot alkaloids may be regarded as the first group of a general pattern of such distorted polypeptides encountered in the gramicidins, penicillins and other antibiotics. Another field of investigation entered by Dr. Jacobs was the chemistry of the aconite alkaloids, which embraced a large group of substances of undetermined structure when he began his inquiry in 1936. Some of these had long been used in medicine, and in some cases are among the most poisonous substances known. These studies included the known aconitine from Aconitum napellus, commonly known as monkshood or wolfsbane, and the isolation of three new alkaloids- heteratisine, hetisine and benzoylheteratisine-as 256 BIOGRAPHICAL MEMOIRS well as the known atisine from Aconitum heterophyllurn Wall. Closely related were delphinine and staphisine from Del- phinium stuphisagfia, similar in action to aconitine. Degrada- tion procedures supplemented by syntheses were reported in some thirty-five communications, until the time of Jacobs' retirement in 1957. The final group of natural products to which Jacobs turned his attention embraces a complex family now known as the steroid bases, or veratrum alkaloids, found in various Veratrum species. These fall into two classes, as suggested by Fieser and Fieser*: the jerveratrum alkamines and the ceveratrum alkamines which comprise cevine and its precursors. Of the first group, Jacobs and co-workers established that rubijervine is a hydroxyl derivative of the known solmidine by conversion to the latter sabstance. Assignment of the hydroxyl group to the 12-position was established by infrared and rotatory dispersion data. A structure for veratramine was also proposed, which was essentially correct except for one minor detail. As with the saponins, interest in jervine increased with recognition of the possibility that it could serve as a starting material for the synthesis of cortisone, and it attracted extensive attention from industrial laboratories. In 1949, Jacobs had tentatively suggested a structure for jervine based on available data for this complex molecule at that time. This was shown to be in error in some respects, although in general it reflected the data then available. The accepted structure was eventually proposed by a group at the Squibb Laboratories. The ceveratrum alkamines generally occur as eslters of various acids. Four of the alkamine bases commonly found as such esters are veracevine, germine, protoverine and zyga- denine. On alkaline hydrolysis, cevine, now recognized as an

*Louis F. Fieser and Mary Fieser, Stmod (New York: Reinhold Publishing Corp., 1959), 11 18 pp. WALTER ABRAHAM JACOBS 257 artifact, was formed from all four. It appeared to be a logical candidate for structural studies in 1937, when Jacobs' long series of studies of these substances began. Selenium dehydrogenation yielded nine bases, five hydrocarbons and one tricyclic phenol. From study of these fragments and spectro- scopic data, it was possible to formulate the ring system of cevine. A second approach involved chromic acid oxidation of cevine which yielded a mixture of acids and lactams from which six pure acidic compounds were isolated by fractional separation of the methyl esters. Heating of the mixture of oxidation products at 200" resulted in the formation of decevinic acid. Data obtained with this substance resulted in corroboration of the structures assigned to other members of this family. The investigations of Jacobs on the veratrum alkaloids continued for some twenty years until his retirement, and formed the basis for more extensive studies of these struc- turally very complicated molecules by other workers. Walter Jacobs was a very highly regarded member of the Rockefeller Institute for some fifty years. His modesty, shy- ness and lack of aggressive tendencies kept even his col- leagues at the Institute from realizing his innate abilities. He showed extraordinary judgment of the correctness and reli- ability of a chemical procedure, and an amazing ability to make most efficient use of time, especially in starting some- thing new when another reaction had to be left for some hours. He insisted on complete and repeated experimental verification before publication of any result, a conservatism which in certain instances resulted in loss of priority. He was not only an excellent and original organic chemist but also a very kind person, and most considerate of his fellow workers. He was fortunate in having married Laura Dreyfoos in 1908. She was the ideal understanding and sup- 25 8 BIOGRAPHICAL MEMOIRS pc~rtivewife for a retiring and dedicated scientist. A warm, outgoing, and capable woman, she furthered in unobtrusive ways the communication of his personality to friends. They often entertained his younger associates in their home in Mount Vernon. He specialized in very temperamental rendi- tions of Beethoven on the Pianola, and in directing record- ings of Wagner's Ring operas. The Jacobs had two children, Elizabeth and Walter, Jr. He was granted emeritus status at the Rockefeller in 1949, but continued active laboratory work until 1957, when he retired and migrated to Los Angeles. WALTER ABRAHAM JACOBS HONORS AND DISTINCTIONS

AWARDS Belgian Order of Leopold 11, 1953

PROFESSIONAL AND HONORARY SOCIETIES National Academy of Sciences (elected, 1932) American Association for the Advancement of Science American Chemical Society American Society of Biological Chemists American Society of Pharmacology and Experimental Thera- peutics Harvey Society BIOGRAPHICAL MEMOIRS BIBLIOGRAPHY

With E. Fischer. Spaltung des racemischen Serins in die optisch- aktiven Componenten. Ber, Dtsch. Chem. Ges., 39:2942.

With J. A. Mandel and P. A. Levene. On nucleic acids. Proc. Soc. Exp. Biol. Med., 5:92-94. With E. Fischer. ~berdie optisch-aktiven Formen des Serins, Isose- rins und Diaminopropionsaure. Ber. Dtsch. Chem. Ges., 40:1057-70.

With P. A. Levene. Zur Gewinnung des Isoleucins aus Eiweiss- spaltungsprodukten. Biochem. Z., 9:231-32. With P. A. Levene. On glycothionic acid. J. Exp. Med., 10:557-58. With P. A. Levene. ~berdie Inosindure. Ber. Dtsch. Chem. Ges., ,41:2703-7. 1909 With P. A. Levene. Further studies on the constitution of inosinic acid. Proc. Soc. Exp. Biol. Med., 6:90. With P. A. Levene. ~berInosinsaure. 11. Mitteilung. Ber. Dtsch. Chem. Ges., 42:335-37. With P. A. Levene. ~berInosinsaure. 111. Mitteilung. Ber. Dtsch. Chem. Ges., 42:1198-1203. With P. A. Levene. ~berdie Pentose in den Nucleinsauren. Ber. Dtsch. Chem. Ges., 42:2102-6. With P. A. Levene. ~berGuanylsaure. I. Mitteilung. Ber. Dtsch. Chem. Ges., 42:246%73. With P. A. Levene. ~berdie Hefe-nucleindure. Ber. Dtsch. Chem. Ges., 42:2474-78. With P. A. Levene. ~berdie Hefe-nucleinsaure. 11. Mitteilung. Ber. Dtsch. Chem. Ges., 42:2703-6. 1910 With P. A. Levene. ~berdie Hefe-nucleinsaure. 111. Mitteilung. Ber. Dtsch. Chem. Ges., 43:3150-63. With P. A. Levene. ~berdie Hexosen aus der d-Ribose. Ber. Dtsch. Chem. Ges.. 43:314147. WALTER ABRAHAM JACOBS 26 1 With P. A. Levene. ~berdie Pankreas-Pentose. Ber. Dtsch. Chem. Ges., 43: 3 147-50. With P. A. Levene. ~berdas Vorkommen des freien Guanosins in der Pankreasdriise. Biochem. Z., 28: 127-30. With P. A. Levene. On yeast nucleic acid. Proc. Soc. Exp. Biol. Med., 7:89-90.

With P. A. Levene. ~berdie Inosinsaure. IV. Ber. Dtsch. Chem. Ges., 44:746-53. With P. A. Levene. ~berdie Hefe-nucleinsiure. IV. Ber. Dtsch. Chem. Ges., 44:1027-32.

Chemical constitution and physiological action. Med. Rec., 81:796. With P. A. Levene and F. Medigreceanu. On the action of tissue extracts containing nucleosidase on a- and P-methylpentosides. J. Biol. Chem., 11:371-80. With P. A. Levene. On sphingosine. J. Biol. Chem., 11:547-54. With P. A. Levene. Guaninehexoside obtained on hydrolysis of thymus nucleic acid. J. Biol. Chem., 12:377-79. With P. A. Levene. On cerebronic acid. J. Biol. Chem., 12:381-88. With P. A. Levene. On the cerebrosides of the brain tissue. J. Biol. Chem., 12:389-98. With P. A. Levene. On the structure of thymus nucleic acid. J. Biol. Chem., 12:411-20. With P. A. Levene. On guanylic acid. Second paper. J. Biol. Chem., l2:42 1-26. On the preparation of glucosides. J. Biol. Chem., 12:427-28. A note of the removal of phosphotungstic acid from aqueous solu- tions. J. Biol. Chem., 12:429-30.

With M. Heidelberger. Mercury derivatives of aromatic amines. I. Structure of primary and secondary p-aminophenylmercuric compounds. Proc. Natl. Acad. Sci. USA, 1:195-96. With M. Heidelberger. On a new group of bactericidal substances obtained from hexamethylenetetramine. Proc. Natl. Acad. Sci. USA, 1:226-28. With M. Heidelberger. Mercury derivatives of aromatic amines. I. 26:! BIOGRAPHICAL MEMOIRS Contribution to the structure of primary and secondary p-aminophenylmercuric compounds. J. Biol. Chem., 20:513-20. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. I. Substituted benzyl halides and the hexamethylenetetraminium salts derived therefrom. J. Biol. Chem., 20:659-83. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. 11. Monohalogenacetylbenzylamines and their hexamethylenetetraminium salts. J. Biol. Chem., 20:685-94. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. 111. Monohalogenacylated aromatic amines and their hexamethylenetetraminium salts. J. Biol. Chem., 2 1: 10343. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. IV. Monohalogenacylated simple amines, ureas, and urethanes, and the hexamethylenetetraminium salts derived therefrom. J. Biol. Chem., 2 1: 145-52. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. V. Monohalogenacetyl derivatives of aminoal~cohols and the hexamethylenetetraminium salts derived therefrom. J. Biol. Chem., 2 1:403-37. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. VI. Halogenethyl ethers and esters and their hexamethylenetetraminium salts. J. Biol. Chem., 2 1:434-53. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. VII. o-Halogen derivatives of aliphatic-aromatic ketones and their hexamethylenetetraminium salts. J. Biol. Chem., 2 1:455-64. With M. Heidelberger. The quaternary salts of hexamethylenetetramine. VIII. Miscellaneous substances containing aliphati- cally bound halogen and the hexamethylenetetraminiunn salts derived therefrom. J. Biol. Chem., 2 1:465-75.

The bactericidal properties of the quaternary salts of hexannethy- lenetetramine. I. The problem of the chemotherapy of experimental bacterial infections. J. Exp. Med., 23:563-68. With M. Heidelberger and H. L. Amoss. The bactericidal properties of the quarternary salts of hexamethylenetetramine. 11. The relation between constitution and bactericidal action iin the substituted benzylhexamethylenetetraminium salts. J. Exp. Med., 23:569-76. WALTER ABRAHAM JACOBS 26: With M. Heidelberger and C. G. Bull. The bactericidal propertie: of the quarternary salts of hexamethylenetetramine. 111. Tht relation between constitution and bactericidal action in the qua ternary salts obtained from halogenacetyl compounds. J. Exp Med., 23:577-99. With P. A. Levene. Note on the hydrolysis of yeast nucleic acid ir the autoclave. J. Biol. Chem., 25: 103.

With M. Heidelberger. The ferrous sulfate and ammonia method for the reduction of nitro to amino compounds. J. Am. Chem SOC.,39: 1435-39. With M. Heidelberger. Methods for the acylation of aromatic amino compounds and ureas, with especial reference to chloro- acetylation. J. Am. Chem. Soc., 39:143947. With M. Heidelberger. Unsymmetrical derivatives of aromatic di- amines. J. Am. Chem. Soc., 39:144745. With M. Heidelberger. The preparation of P-chloro- and P-bromopropionic acids. J. Am. Chem. Soc., 39: 1465-66. With M. Heidelberger. On nitro- and amino-phenoxyacetic acids. J. Am. Chem. Soc., 39:2188-224. With M. Heidelberger. On amides, uramino compounds, and ureides containing an aromatic nucleus. J. Am. Chem. Soc., 39:241843.

With W. H. Brown, M. Heidelberger, and L. Pearce. N-(p- Arsonopheny1)-glycinamideand similar compounds. U. S. patent 1,280,119, 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. N-Phenyl- glycin-P-methylureidolb-arsonicacid and similar arsenic compounds. U. S. patent 1,280,120. 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. N-(p- Arsonopheny1)-glycyl-m-aminophenoland similar arsenic compounds. U. S. patent 1,280,121. 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. N- (Arsinosopheny1)-glycylaminophenoland similar arsenic compounds. U. S. patent 1,280,122. 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. N-(p- 264 BIOGRAPHICAL MEMOIRS Arsenopheny1)-bisglycyl-m-aminophenol and similar arsenic compounds. U. S. patent 1,280,123. 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. Sodium N- phenylglycin-amide-p-arsonateand similar arsenic compourtds. U. S. patent 1,280,124. 24 Sept. 1918. With W. H. Brown, M. Heidelberger, and L. Pearce. Sodium salts of organic arsenic compounds. U. S. patent 1,280,126. 24 Sept. 1918. 1919 With M. Heidelberger and I. P. Rolf. On certain aromatic amines and chloroacetyl derivatives. J. Am. Chem. Soc., 4 1:458-74. With M. Heidelberger. Syntheses in the cinchona series. I. The simpler cinchona alkaloids and their dihydro derivatives. J. Am. Chem. Soc., 41 :817-33. With M. Heidelberger. The isomeric hydroxyphenylarsonic acids and the direct arsonation of phenol. J. Am. Chem. Soc., 41 1440. With M. Heidelberger. Certain amino and acylamino phenol ethers. J. Am. Chem. Soc., 41: 1450-72. With M. Heidelberger. Aromatic arsenic compounds. I. A plan of procedure for the synthesis of arsenicals for chemotherapeutic research. J. Am. Chem. Soc., 41 : 1581-87. With M. Heidelberger. Aromatic arsenic compounds. 11. The amides and alkylamides of N-arylglycine arsonic acids. J. Am. Chem. Soc., 4 1: 1587-600. With M. Heidelberger. Aromatic arsenic compounds. 111. The ureides and /?-substituted ureides of N-arylglycine arsonic acids. J. Am. Chem. Soc., 41: 1600-1610. With M. Heidelberger. Aromatic arsenic compounds. IV. Aromatic amides of N-arylglycine arsonic acids. J. Am. Chem. Soc., 41:161044. With M. Heidelberger. Aromatic arsenic compounds. V. N- Substituted glycylarsanilic acids. J. Am. Chem. Soc., 41 1809-21. With M. Heidelberger. Aromatic arsenic compounds. VI. N- (Phenyl-4-arsonic acid)-a-phenylglycine and its amides. J. Am. Chem. Soc., 41: 1822-25. With M. Heidelberger. Aromatic arsenic compounds. VII. Substi- tuted benzyl, phenoxyethyl and phenacylarsanilic acids. J. ALm. Chem. Soc., 41 : 1826-33. WALTER ABRAHAM JACOBS 265 With M. Heidelberger. Aromatic arsenic compounds. VIII. The amides of (4-arsonic acid)-phenoxyacetic acid and the isomeric phenoxy-acetylarsanilic acids. J. Am. Chem. Soc., 4 1: 183440. With M. Heidelberger. Syntheses in the cinchona series. 11. Quater- nary salts. J. Am. Chem. Soc., 41:2090-120. With M. Heidelberger. Syntheses in the cinchona series. 111. Azo dyes derived from hydrocupreine and hydrocupreidine. J. Am. Chem. Soc., 41:213147. With M. Heidelberger. Chemotherapy of trypanosome and spiro- chete infections. Chemical series. I. N-PhenylglycineamideP- arsonic acid. J. Exp. Med., 30:411-15. With M. Heidelberger. On N-phenylglycineamideP-arsonic acid. J. Pharm. Exp. Therap., 13:501-2. With W. H. Brown, M. Heidelberger and L. Pearce. Organic arsenic compounds. U. S. patent 1,315,127. 2 Sept. 1919. 1920 With M. Heidelberger. Syntheses in the cinchona series. IV. Nitro and amino derivatives of the dihydro alkaloids. J. Am. Chem. SOC.,42: 1481-89. With M. Heidelberger. Syntheses in the cinchona series. V. Dihy- drodesoxyquinine and dihydrodesoxyquinidine and their derivatives. J. Am. Chem. Soc., 42:148%502. With M. Heidelberger. Syntheses in the cinchona series. VI. Aminoazo and hydroxyazo dyes derived from certain 5-amino cinchona alkaloids and their quinoline analogs. J. Am. Chem. SOC.,42:2278-86. 1921 With M. Heidelberger. Aromatic arsenic compounds. IX. Diazo- amino compounds of arsanilic acid and its derivatives. J. Am. Chem. Soc., 43: 1632-45. With M. Heidelberger. Aromatic arsenic compounds. X. Azo dyes derived from arsanilic acid. J. Am. Chem. Soc., 43: 1646-54. 1922 With M. Heidelberger. Strophanthin. I. Strophanthidin. J. Biol. Chem., 54:253-61. With M. Heidelberger. Syntheses in the cinchona series. VII. 5,8-Diamino-dihydroquinineand 5,8-diamino-6-methoxyquin- oline and their conversion into the corresponding aminohy- droxy and dihydroxy bases. J. Am. Chem. Soc., 44: 1073-79. 266 BIOGRAPHICAL MEMOIRS With M. Heidelberger. Syntheses in the cinchona series. VIII. The hydrogenation of dihydrocinchonine, cinchonine and dihyclro- quinine. J. Am. Chem. Soc., 44:1079-90. With M. Heidelberger. Syntheses in the cinchona series. IX. Cer- tain quinicine and benzoylcinchona salts, crystalline ethyl dihy- drocupreine (Optochin) base and other derivatives. J. Am. Chem. Soc., 44: 1091-98. With M. Heidelberger. Syntheses in the cinchona series. X. Dihy- drocinchonicinol and the dihydroquinicinols. J. Am. Chem. SOC.,44: 1098-107. With M. Heidelberger. Certain triphenylmethane dyes. J. Am. Chem. Soc., 44:262&28. 1923 Strophanthin. 11. The oxidation of strophanthidin. J. Biol. Chem., 57:553-67. Strophanthin. 111. Crystalline Kombe strophanthin. Preliminary note. J. Biol. Chem., 57:569-72. The chemotherapy of protozoan and bacterial infections. Harvey Lectures, 19:67-95. 1924 Certain aspects of the chemotherapy of protozoan and bacterial infections. Medicine, 3 :165-93. With A. M. Collins. Strophanthin. IV. Anhydrostrophanthidin and dianhydrostrophanthidin. J. Biol. Chem., 59:713-30. With A. M. Collins. Strophanthin. V. The isomerization and oxidation of isostrophanthidin. J. Biol. Chem., 6 1:387-403.

With A. M. Collins. Strophanthin. VI. The anhydrostrophanthidins anld their behavior on hydrogenation. J. Biol. Chem., 63:123-33. Saponins. I. The sapogenin obtained from soapnuts. J. Biol. Chem., 63:621-29. Saponins. 11. On the structure of hederagenin. J. Biol. Chem., 63 :63 140. Saponins. 111. The sapogenin occurring in the Sapindus saponaria L. and Sapindus mukorossi utilis (Trabuti). J. Biol. Chem., 64:379-8 1. With .A. M. Collins. Strophanthin. VII. The double bond of strophanthidin. J. Biol. Chem., 64:383-89. WALTER ABRAHAM JACOBS 267 With A. M. Collins. Strophanthin. VIII. The carbonyl group of strophanthidin. J. Biol. Chem., 65:491-505. With A. Hoffmann. A structural characteristic of the cardiac poisons. Proc. Soc. Exp. Biol. Med., 23:213-15.

With A. Hoffmann. The structural relationship of the cardiac poisons. J. Biol. Chem., 67:333-39. With A. Hoffmann. Strophanthin. IX. On crystalline Kombe strophanthin. J. Biol. Chem., 67:609-20. With A. Hoffmann. Strophanthin. X. On K-strophanthin-/3 and other Kombe strophanthins. J. Biol. Chem., 69:15343. With E. L. Gustus. Saponins. IV. The oxidation of hederagenin methyl ester. J. Biol. Chem., 69:641-52. With E. L. Gustus, The association of the double bond with the lactone group in the cardiac aglucones. J. Biol. Chem., 70: 1-1 1.

With M. Heidelberger. Chloroacetamide. Org. Synth., 7:16-17. With A. Hoffmann. The relationship between the structure and the biological action of the cardiac glucosides. J. Biol. Chem., 74:787-94. With E. L. Gustus. Strophanthin. XI. The hydroxyl groups of strophanthidin. J. Biol. Chem., 74:795-804. With E. L. Gustus. Strophanthin. XII. The oxidation of trianhydro- strophanthidin. J. Biol. Chem., 74:805-10. With E. 1,. Gustus. Strophanthin. XIII. Isostrophanthidin and its derivatives. J. Biol. Chem., 74:81 1-27. With E. L. Gustus. Strophanthin. XIV. Isomerization in the isostrophanthidin series. J. Biol. Chem., 745329-37.

With M. Heidelberger. Sodium p-arsono-N-phenylglycinamide (Tryparsamide). Org. Synth., 8:100-101. With E. L. Gustus. The digitalis glucosides. I. Digitoxigenin and isodigitoxigenin. J. Biol. Chem., 78:573-81. With A. Hoffmann. Periplocymarin and periplogenin. J. Biol. Chem., 79:519-30. With A. Hoffmann. Strophanthin. XV. Hispidus strophanthin. J. Biol. Chem., 79:531-37. 268 BIOGRAPHICAL MEMOIRS With E. L. Gustus. Strophanthin. XVI. Degradation in the isostrophanthidin series. J. Biol. Chem., 79:539-52. With E. L. Gustus. The digitalis glucosides. 11. Gitoxigenin and isogitoxigenin. J. Biol. Chem., 79:553-62.

With M. Heidelberger. Sarmentocymarin and sarmentogenin. J. Biol. Chem., 8 1 :765-79. With E. L. Gustus. The digitalis glucosides. 111. Gitoxigenin and isogitoxigenin. J. Biol. Chem., 82:403-9. With E. L. Gustus. Strophanthin. XVII. Dehydration and lactone cleavage in isostrophanthic acid derivatives. J. Biol. Chem., 84 :183-90. With E. L. Gustus. The structural correlation of gitoxigenin with digitoxigenin. Science, 70:63940.

With E. L. Gustus. The digitalis glucosides. IV. The correlation of gitoxigenin with digitoxigenin. J. Biol. Chem., 86: 199-2 16. With A. B. Scott. The hydrogenation of unsaturated lactones to desoxy acids. J. Biol. Chem., 87:601-13. With E. E. Fleck. The partial dehydrogenation of a- and p-amyrin. J. Biol. Chem., 88:137-52. With E. E. Fleck. Saponins. V. The partial dehydrogenation of hederaginin. J. Biol. Chem., 88: 153-61. Strophanthidin. XVIII. Allocymarin and allostrophanthidin. An enzymatic isomerization of cymarin and strophanthidin. J. Biol. Chem., 88:519-29. With E. L. Gustus. The digitalis glucosides. V. The oxidation and isomerization of gitoxigenin. J. Biol. Chem., 88:53144. With E. E. Fleck. Tigogenin, a digitalis sapogenin. J. Biol. Chem., 88:545-50.

With R. C. Elderfield, T. B. Grave, and E. W. Wignall. Strophan- thin. XX. The conversion of isostrophanthidic acid into the desoxo derivative. J. Biol. Chem., 91 :6 17-23. With R. C. Elderfield. Strophanthin. XXI. The correlation of strophanthidin and periplogenin. J. Biol. Chem., 91 :625-28. With R. C. Elderfield. Strophanthin. XXII. The correlation of stro- WALTER ABRAHAM JACOBS 269 phanthidin and periplogenin with digitoxigenin and gitoxigenin. J. Biol. Chem., 92:s 13-2 1. With E. L. Gustus. Strophanthin. XXIII. Ring I1 of strophanthidin and of related aglucones. J. Biol. Chem., 92:32344. With E. E. Fleck. The partial dehydrogenation of ursolic acid. J. Biol. Chem., 92:487-94. With R. C. Elderfield, A. Hoffmann, and T. B. Grave. Strophan- thin. XXIV. Isomeric hexahydrodianhydrostrophanthidins and their derivatives. J. Biol. Chem., 93: 127-38. With A. B. Scott. The hydrogenation of unsaturated lactones to desoxy acids. 11. J. Biol. Chem., 93: 139-52. Phoebus A. Levene-The man. Chem. Bull., 18:121. With E. E. Fleck. Strophanthin. XIX. The dehydrogenation of strophanthidin and gitoxigenin. Science, 73 : 133-34.

With E. E. Fleck. The partial dehydrogenation of oleanolic acid. J. Biol. Chem., 96:341-54. With N. M. Bigelow. The sugar of sarmentocymarin. J. Biol. Chem., 96:355. With R. C. Elderfield. Strophanthin. XXV. The allocation of the lactone group of strophanthidin and related aglucones. J. Biol. Chem., 96:357-66. With N. M. Bigelow. Ouabain or g-strophanthin. J. Biol. Chem., 96:647-58. With E. E. Fleck. Strophanthin. XXVI. A further study of the dehydrogenation of strophanthidin. J. Biol. Chem., 97:57-61. With R. C. Elderfield. Strophanthin. XXVII. Ring I11 of strophanthidin and related aglucones. J. Biol. Chem., 97:727-37. The ergot alkaloids. I. The oxidation of ergotinine. J. Biol. Chem., 97:739-43.

With N. M. Bigelow. The strophanthins of Strophanthus eminii. J. Biol. Chem., 99:521-29. With R. C. Elderfield. The digitalis glucosides. VI. The oxidation of anhydrodihydrodigitoxigenin. The problem of gitoxigenin. J. Biol. Chem., 99:693-99. With R. C. Elderfield. The digitalis glucosides. VII. The isomeric dihydrogitoxigenins. J. Biol. Chem., 100:67 1-83. 270 BIOGRAPHICAL MEMOIRS With N. M. Bigelow. Ouabain. 11. The degradation of isoouabain. J. Biol. Chem., 101:15-20. With N. M. Bigelow. Trianhydroperiplogenin. J. Biol. Chem., 101 :697-700. With R. C. Elderfield. Strophanthin. XXVIII. Further degradation of strophanthidin and periplogenin derivatives. J. Biol. Chem., 102:23748. The chemistry of the cardiac glucosides. Physiol. Rev., 13:222-45.

With I,. C. Craig. The ergot alkaloids. 11. The degradation of ergotinine with alkali. Lysergic acid. J. Biol. Chem., lO4:M7-5 1. With R. C. Elderfield. The digitalis glucosides. VIII. The degradation of the lactone side chain of digitoxigenin. Science, 80:434. With J. C. E. Simpson. On sarsasapogenin and gitogenin. J. Biol. Chem., 105:501-10. With L. C. Craig. The ergot alkaloids. 111. On lysergic acid. J. Biol. Chem., 106:393-99. With R. C. Elderfield. Strophanthin. XXIX. The dehydrogenation of strophanthidin. Science, 79:279-80. With R. C. Elderfield. Strophanthin. XXXI. Further studies on the dehydrogenation of strophanthidin. J. Biol. Chem., 107: 143-54. With R. C. Elderfield. The structure of the cardiac glucosicles. Science, 80:533-34.

With R. C. Elderfield. The structure of the cardiac aglucones. J. Bid. Chem., 108:497-513. With L. C. Craig. The ergot alkaloids. IV. The cleavage of ergotinine with sodium and butyl alcohol. J. Biol. Chem., 108:595406. With R. C. Elderfield. Strophanthin. XXXII. The anhydrostrophanthidins. J. Biol. Chem., 108:693-702. With J. C. E. Simpson. Sarsasapogenin. 11. J. Biol. Chem., 109:573-84. With J. C. E. Simpson. The digitalis sapogenins. J. Biol. Chem., 110:429-38. WALTER ABRAHAM JACOBS 27 1 With L. C. Craig. The ergot alkaloids. V. The hydrolysis of ergotinine. J. Biol. Chem., 110:521-30. With J. C. E. Simpson. Sarsasapogenin. 111. Desoxysarsasapogenin. Further degradations of sarsasapogenin. J. Biol. Chem., 110:565-73. With L. C. Craig. The ergot alkaloids. VI. Lysergic acid. J. Biol. Chem., 11 1 :455-65. With L. C. Craig. The structure of the ergot alkaloids. J. Am. Chem. Soc., 57:383-84. With L. C. Craig. The hydrolysis of ergotinine and ergoclavine. J. Am. Chem. Soc., 57:960-61. With L. C. Craig. The ergot alkaloids. Science, 81:25&57. With L. C. Craig. On an alkaloid from ergot. Science, 82:16-17. With L. C. Craig. The ergot alkaloids. Synthesis of 4-carboline carbonic acids. Science, 82:42 1-22. 1936 With R. C. Elderfield. Strophanthin. XXXIII. The oxidation of anhydroaglucone derivatives. J. Biol. Chem., 1l3:6 11-24. With R. C. Elderfield. Strophanthin. XXXIV. Cyanhydrin syntheses with dihydrostrophanthidin and derivatives. J. Biol. Chem., 113:625-30. With L. C. Craig. The ergot alkaloids. VIII. The synthesis of 4-carboline carbonic acids. J. Biol. Chem., 113:759-65. With L. C. Craig. The ergot alkaloids. IX. The structure of lysergic acid. J. Biol. Chem., 113:767-78. With R. C. Elderfield. The lactone group of the cardiac aglycones and Grignard reagent. J. Biol. Chem., 114:597-99. With L. C. Craig. The ergot alkaloids. XI. Isomeric dihydrolysergic acids and the structure of lysergic acid. J. Biol. Chem., 115:227-38. With R. C. Elderfield. The N-alkyl group of aconine (aconitine). J. Am. Chem. Soc., 58:1059. With L. C. Craig. The ergot alkaloids. X. On ergotamine and ergoclavine. J. Org. Chem., 1:245-53. With L. C. Craig. The ergot alkaloids. The structure of lysergic acid. Science, 83:38-39. With I,. C. Craig and A. Rothen. The ergot alkaloids. The ultraviolet absorption spectra of lysergic acid and related substances. Science, 83: 166-67. 272 BIOGRAPHICAL MEMOIRS

With L. C. Craig. The veratrine alkaloids. I. The degradation of cevine. J. Biol. Chem., 119:141-53. With 0.Isler. The sapogenins of Polygala senega. J. Biol. Chem., 119: 155-70. With R. G. Gould. The ergot alkaloids. XII. The synthesis of substances related to lysergic acid. J. Biol. Chem., 120:141-50. With L. C. Craig. The veratrine alkaloids. 11. Further study of the basic degradation products of cevine. J. Biol. Chem., 120:447-56. With R. G. Gould. The synthesis of substances related to lysergic acid. Science, 85:248-49.

With L. C. Craig. The ergot alkaloids. XIII. The precursors of pyruvic and isobutyrylformic acids. J. Biol. Chem., l22:419-23. With L. C. Craig. The veratrine alkaloids. 111. Further studies on the degradation of cevine. The question of coniine. J. Biol. Chem., 124:659-66. With L. C. Craig, T. Shedlovsky, and R. G. Gould. The ergot alkaloids. XIV. The positions of the double bond and the carboxyl group in lysergic acid and its isomer. The structure of the al!ka- loids. J. Biol. Chem., 125:289-98. With L. C. Craig. The veratrine alkaloids. IV. The degradation of cevine methiodide. J. Biol. Chem., 125:625-34. With R. G. Gould. The ergot alkaloids. XVI. Further studies of the synthesis of substances related to lysergic acid. J. Biol. Chem., 126:67-76. With L. C. Craig. The position of the carboxyl grmp in lysergic acid. J. Am. Chem. Soc., 60:1701-2. With R. C. Elderfield. The terpenes, saponins and closely related compounds. Annu. Rev. Biochem., 7:449-72.

With L. C. Craig. Delphinine. J. Biol. Chem., 127:361-66. With L. C. Craig. Delphinine. 11. On oxodelphinine. J. Biol. Chem., l28:431-37. With R. C. Elderfield and L. C. Craig. The aconite alkaloids. 11. The formula of oxonitine. J. Biol. Chem., 128:439-46. WALTER ABRAHAM JACOBS 273 With L. C. Craig. The ergot alkaloids. XVII. The dimethylindole from dihydrolysergic acid. J. Biol. Chem., l28:7 15-1 9. With L. C. Craig. The veratrine alkaloids. V. The selenium dehydrogenation of cevine. J. Biol. Chem., 129:79-87. With R. G. Gould. The ergot alkaloids. XVIII. The production of a base from lysergic acid and its comparison with synthetic 6,8-dimethylergoline. J. Biol. Chem., 130:39%405. With R. G. Gould. The preparation of certain trimethyleneindole derivatives. J. Biol. Chem., 130:407-14. With L. C. Craig. The veratrine alkaloids. VI. The oxidation of cevine. J. Am. Chem. Soc., 61:2252-53. With R. G. Gould. The synthesis of certain substituted quinolines and 5,6-benzoquinolines. J. Am. Chem. Soc., 61 :2890-95.

With L. C. Craig. The veratrine alkaloids. VII. On decevinic acid. J. Biol. Chem., 134: 123-35. With L. C. Craig. Delphinine. 111. The action of hydrochloric, nitric and nitrous acids on delphinine and its derivatives. J. Biol. Chem., l36:303-2 1. With L. C. Craig. The aconite alkaloids. 111. The oxidation of aconitine and derivatives with nitric acid and chromic acid. J. Biol. Chem., 136:323-34.

With L. C. Craig. The veratrine alkaloids. VIII. Further studies on the selenium dehydrogenation of cevine. J. Biol. Chem., 139:263-75. With L. C. Craig and G. I. Lavin. The veratrine alkaloids. IX. The nature of the hydrocarbons from the dehydrogenation of cevine. J. Biol. Chem., l39:277-91. With L. C. Craig. The veratrine alkaloids. X. The structure of ceventhridine. J. Biol. Chem., 139:293-99. With D. D. Van Slyke. Phoebus Aaron Theodor Levene. J. Biol. Chem., 141:l-2. With L. C. Craig and G. I. Lavin. The veratrine alkaloids. XI. The dehydrogenation of jervine. J. Biol. Chem., 14 1:5 1-66. With L. C. Craig. The aconite alkaloids. VII. On staphisine, a new alkaloid from Delphinium stuphisagnu. J. Biol. Chem., 14 1:67-84. 274 BIOGRAPHICAL MEMOIRS With L. C. Craig. The veratrine alkaloids. XII. Further studies on the oxidation of cevine. J. Biol. Chem., 14 1:253-67. The chemistry of the ergot alkaloids. In: Bicentennial Conference. Chemical Kinetics and Natural Products, pp. 2741. Philadelphia: Univ. of Pennsylvania Press.

With L. C. Craig. The veratrine alkaloids. XIII. The dehydrogenation of protoveratrine. J. Biol. Chem., 143:427-32. With L. C. Craig. The aconite alkaloids. VIII. On atisine. J. Biol. Chem., 143:598-603. With L. C. Craig. The aconite alkaloids. IX. The isolation of two new alkaloids from Aconitum heterophyllum, heteratisine and het- ishe. J. Biol. Chem., 143:605-9. With L. C. Craig. The aconite alkaloids. X. On napelline. J. IBiol. Chem., 143:611-16. With R. G. Gould and L. C. Craig. The ergot alkaloids. XIX. The transformation of dl-lysergic acid and d-lysergic acid to 6,8-dimethylergolines. J. Biol. Chem., 145:487-94.

With L. C. Craig. The aconite alkaloids. XI. The action of methyl alcoholic sodium hydroxide on atisine. Isoatisine and dihydroatisine. J. Biol. Chem., 147:56749. With L. C. Craig. The aconite alkaloids. XII. Benzoylheteratisine, a new alkaloid from Aconitum heterophyllum. J. Biol. Ch~em., 147:571-72. With L. C. Craig. The veratrine alkaloids. XV. On rubijervine and isorubijervine. J. Biol. Chem., 148:41-50. With L. C. Craig. The veratrine alkaloids. XVI. The formulatiam of jervine. J. Biol. Chem., 148:51-55. With L. C. Craig. The veratrine alkaloids. XVII. On germine. Its formulation and degradation. J. Biol. Chem., 148:57-66. With L. C. Craig. The veratrine alkaloids. XIX. On protoveratrine and its alkamine, protoverine. J. Biol. Chem., 149:271-79 With L. C. Craig. The veratrine alkaloids. XX. Further correlations in the veratrine group. The relationship between the veratrine bases and solanidine. J. Biol. Chem., 149:451-64. With L. C. Craig. The veratrine alkaloids. XIV. The correlation of the veratrine alkaloids with the solanum alkaloids. Science, 97:122. WALTER ABRAHAM JACOBS 275

With L. C. Craig. The veratrine alkaloids. XXI. The conversion of rubijervine to allorubijervine. The sterol ring system of rubijervine. J. Biol. Chem., 152:641-43. With L. C. Craig. The aconite alkaloids. XIII. The isolation of pimanthrene from the dehydrogenation products of staphisine. J. Biol. Chem., 152:645-50. With L. C. Craig. The aconite alkaloids. XIV. Oxidation of the hydrocarbon from the dehydrogenation of atisine. J. Biol. Chem., l52:65 1-57. With L. C. Craig, L. Michaelis, and S. Granick. The aconite alkaloids. XV. The nature of the ring system and character of the nitrogen atom. J. Biol. Chem., 154:293-304. With L. C. Craig. The veratrine alkaloids. XXII. On pseudojervine and veratrosine, a companion glycoside in Veratrum viride. J. Biol. Chem., 155:565. With D. D. Van Slyke. Phoebus Aaron Theodor Levene. In: Bio- graphical Memoirs, 23:75-126. N.Y.: Columbia Univ. Press for the National Academy of Sciences.

With L. C. Craig. The veratrine alkaloids. XXIII. The ring system of rubijervine and isorubijervine. J. Biol. Chem., 159:617-24. With F. C. Uhle. The veratrine alkaloids. XXIV. The octahydro- pyrrocoline ring system of the tertiary bases. Conversion of sarsasapogenin to a solanidine derivative. J. Biol. Chem., 160:24348. With L. C. Craig. The veratrine alkaloids. XXV. The alkaloids of Veratrum viride. J. Biol. Chem., 160:555-65. With F. C. Uhle. The ergot alkaloids. XX. The synthesis of dl- lysergic acid. A new synthesis of 3-substituted quinolines. J. Org. Chem., 10:76-86.

With C. F. Huebner. The aconite alkaloids. XVI. On staphisine and the hydrocarbon obtained from its dehydrogenation. J. Biol. Chem., l69:2 1 1-20. With C. F. Huebner. The veratrine alkaloids. XXVI. On the hex- anetetracarboxylic acid from cevine and germine. J. Biol. Chem., 170: 181-87. 276 BIOGRAPHICAL MEMOIRS With C. F. Huebner. The aconite alkaloids. XVII. Further studies with hetisine. J. Biol. Chem., 170:189-201. With C. F. Huebner. The aconite alkaloids. XVIII. The synthesis of the hydrocarbon obtained on ,dehydrogenation of atisine. J. Biol. Chem., 170:203-7. With C. F. Huebner. The aconite alkaloids. XIX. Further studies with delphinine derivatives. J. Biol. Chem., l70:209-20. With C. F. Huebner. The aconite alkaloids. XX. Further studies with atisine and isoatisine. J. Biol. Chem., 170:s 15-25. With C. F. Huebner. The veratrine alkaloids. XXVII. Further studies with jervine. J. Biol. Chem., 170:635-52.

With C. F. Huebner. The aconite alkaloids. XXI. Further oxidation studies with atisine and isoatisine. J. Biol. Chem., 174: 1001-12. With Y. Sato. The veratrine alkaloids. XXVIII. The structure of jervine. J. Biol. Chem., 175:57-65.

With Y. Sato. The veratrine alkaloids. XXIX. The structure of rubijervine. J. Biol. Chem., 179:623-32. With Y. Sato. The aconite alkaloids. XXII. The demethylation of delphinine derivatives. J. Biol. Chem., 180: 13344. With Y. Sato. The aconite alkaloids. XXIII. Oxidation of iso- pyroxodelphonine, dihydroisopyroxodelphonine and their desmethylanhydro derivatives. J. Biol. Chem., 180:479-94. With Y. Sato. The veratrine alkaloids. XXX. A further study of the structure of veratramine and jervine. J. Biol. Chem., 181 :55-65.

With Y. Sato. The veratrine alkaloids. XXXI. The structure of isorubijervine. J. Biol. Chem., 191:63-69. With Y. Sato. The veratrine alkaloids. XXXII. The structure of veratramine. J. Biol. Chem., 191 :7 1-86. With H. Jaffe. The veratrine alkaloids. XXXIII. 'The isomeric forms of cevine, germine and protoverine. J. Biol. Chlem., 193:325-37. The aconite alkaloids. XXIV. The degradation of atisine and iaoat- isine. J. Org. Chem., 16: 1593402. WALTER ABRAHAM JACOBS 277 1952 With S. W. Pelletier. The veratrine alkaloids. XXXIV. The transformation of isorubijervine to solanidine. J. Am. Chem. Soc., 74:4218-19.

With S. W. Pelletier. The veratrine alkaloids. XXXV. Veracevine, the alkanolamine of cervadine and veratridine. J. Am. Chem. SOC.,75:3248-52. With S. W. Pelletier. The veratrine alkaloids. XXXVI. A possible skeletal structure for veracevine, cevine and protoverine. J. Org. Chem., 18:765-73. With S. W. Pelletier. The veratrine alkaloids. XXXVII. The structure of isorubijervine. Conversion to solanidine. J. Am. Chem. SOC.,75:444246.

With S. W. Pelletier. The aconite alkaloids. XXV. The oxygen- containing groups of delphinine. J. Am. Chem. Soc., 76: 161-69. With S. W. Pelletier. The veratrine alkaloids. XXXVIII. The ring system of the tertiary polyhydroxy veratrine bases. Oxidative studies with cevanthridine and veranthridine. J. Am. Chem. SOC.,76:2028-29. With S. W. Pelletier. The aconite alkaloids. XXVI. Oxonitine and oxoaconitine. J. Am. Chem. Soc., 76:4048-49. With S. W. Pelletier. The aconite alkaloids. XXVII. The structure of atisine. J. Am. Chem. Soc., 76:449&97.

With S. W. Pelletier. The nature of a-oxodelphinine and fl-oxodelphinine. Chem. Ind., 30:94849. With S. W. Pelletier. The quaternary chlorides and acetates of atisine. Chem. Ind., 43: 1385-87.

With S. W. Pelletier. The veratrine alkaloids. XXXIX. A study of certain selenium dehydrogenation products of cevine. J. Am. Chem. Soc., 78: 1914-18. 278 BIOGRAPHICAL MEMOIRS With S. W. Pelletier. The aconite alkaloids. XXXII. The structure of delphinine. J. Am. Chem. Soc., 78:354243. With S. W. Pelletier. The aconite alkaloids. XXX. Products from the mild permanganate oxidation of atisine. J. Am. Chem. Soc., 78:4 139-43. With S. W. Pelletier. The aconite alkaloids. XXXI. A partiall synthesis of atisine, isoatisine and dihydroatisine. J. Am. Chem. SOC.,78:414445. With S. W. Pelletier. The aconite alkaloids. XXXIII. 'The identity of a-oxodelphinine. J. Org. Chem., 21 : 1514-1 5. 1957 With S. W. Pelletier. The aconite alkaloids. XXXV. Structural studies with delphinine derivatives. J. Org. Chem., 22: 1423-32.

With S. W. Pelletier. The nature of oxonitine. Chem. Ind., %1:591-92.